Title

Improving Viral Protease Inhibitors to Counter Drug Resistance

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2016-04-15

Document Type

Article

Disciplines

Biochemistry | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology | Virology

Abstract

Drug resistance is a major problem in health care, undermining therapy outcomes and necessitating novel approaches to drug design. Extensive studies on resistance to viral protease inhibitors, particularly those of HIV-1 and hepatitis C virus (HCV) protease, revealed a plethora of information on the structural and molecular mechanisms underlying resistance. These insights led to several strategies to improve viral protease inhibitors to counter resistance, such as exploiting the essential biological function and leveraging evolutionary constraints. Incorporation of these strategies into structure-based drug design can minimize vulnerability to resistance, not only for viral proteases but for other quickly evolving drug targets as well, toward designing inhibitors one step ahead of evolution to counter resistance with more intelligent and rational design.

DOI of Published Version

10.1016/j.tim.2016.03.010

Source

Trends Microbiol. 2016 Apr 15. pii: S0966-842X(16)30002-6. doi: 10.1016/j.tim.2016.03.010. [Epub ahead of print] Link to article on publisher's website

Journal/Book/Conference Title

Trends in microbiology

Related Resources

Link to article in PubMed

PubMed ID

27090931

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